Neuropeptide Y activates urocortin 1 neurons in the nonpreganglionic Edinger-Westphal nucleus

Central regulatory pathways promoting stress adaptation utilize various neurotransmitters/neuropeptides, such as urocortin 1 (Ucn1) and neuropeptide Y (NPY). Ucn1 is abundantly expressed in the nonpreganglionic Edinger-Westphal nucleus (npEW), where it is codistributed with NPY-immunoreactive (ir) terminals. A special role for both neuropeptides has been postulated in stress adaptation. Using double-labeling immunohistochemistry, we observed close appositions between NPY-ir terminals and neurons immunoreactive for Ucn1 in the rat, as well as in the human npEW. Therefore, we hypothesized that NPY might control the activity of Ucn1-positive neurons in the npEW. To test this hypothesis, NPY was injected into the lateral cerebral ventricle of rats, resulting in a strong activation of npEW Ucn1 neurons as revealed by Fos immunohistochemistry. Ucn1 mRNA was also upregulated in the npEW 2 hours after the injection of NPY. In a search for the type of NPY receptor that mediates this NPY-induced recruitment of npEW-Ucn1 cells, we found that the great majority of Ucn1 cells exhibited NPY Y5 receptor immunoreactivity, and only a few of the Ucn1 cells coexpressed the Y1 receptor. We concluded that NPY, via NPY Y5 and to a lesser extent via the Y1 receptors, exerts a stimulatory action on Ucn1 cells in the npEW. Further studies are currently in progress to elucidate the significance of this NPY-Ucn1 interaction in the npEW.     

Neuropeptide Y: regional distribution chromatographic characterization and immunohistochemical demonstration in post-mortem human brain

Using a neuropeptide Y (NPY)-directed radioimmunoassay the post-mortem stability of NPY was assessed in both rat and human brain samples. The regional distribution of NPY-like immunoreactivity in human brain was determined. The NPY-like immunoreactivity in human brain separated on Sephadex G-50 columns and ¹⁸C reverse phase at the position expected for NPY. Immunohistochemical staining using the NPY-directed antiserum revealed a characteristic population of cortical and striatal neurons containing NPY-like immunoreactivity.     

脑出血大鼠脑组织神经肽Y水平的变化及意义

目的 :探讨脑出血过程中中枢神经系统神经肽Y(NPY)含量的动态变化及意义。方法 :采用胶原酶和肝素联合注入尾状核的方法建立大鼠脑出血模型 ,测定出血前、出血后 30min ,6、1 2、2 4、48及 72h血肿周边、下丘脑及脑干NPY的活性。结果 :脑出血后血肿周边、下丘脑及脑干NPY的含量同步升高 ,并于 2 4h达峰值 ,48～ 72h开始回落 ,但仍显著高于出血前 (P <0 0 1 )。结论 :脑出血过程中 ,脑组织NPY活性增强 ,导致局部脑血流量减少 ,最终加重神经细胞损害     

A comparison of regional somatostatin and neuropeptide Y distribution in rat striatum and brain

Somatostatin-like immunoreactivity (SLI) and neuropeptide Y-like immunoreactivity (NPYLI) were detected using specific radioimmunoassays in extracts from rat brain. Since we have previously found a topographic distribution of SLI in rat striatum the distribution of NPYLI was examined in the same regions. NPYLI showed an identical distribution to SLI in rat striatum and levels were significantly correlated (r = 0.93, P less than 0.01). Concentrations of both neuropeptides were consistently highest in ventromedial striatum and nucleus accumbens while they were lowest in dorsolateral striatum. These findings provide further evidence of neurochemical heterogeneity in the striatum. Concentrations of NPYLI and SLI were also significantly correlated in cerebral cortex (r = 0.99, P less than 0.01). Concentrations of NPYLI were generally higher than SLI and showed a similar predilection for limbic system nuclei. The present findings support the concept that somatostatin and neuropeptide Y may be co-localized in both striatal and cortical neurons.     

Metabotropic Glutamate Receptor 2 and 3 Gene Expression in The Human Prefrontal Cortex and Mesencephalon in Schizophrenia

Group II metabotropic glutamate receptors (mGluR2 and mGluR3) are implicated in schizophrenia. We characterized mGluR2 and 3 mRNA in the human prefrontal cortex (PFC) and mesencephalon, and then compared cases with schizophrenia to matched controls. In the human brain, both receptors were expressed in the PFC and, unlike the rodent, in dopaminergic (DA) cell groups. In schizophrenia, we found significantly higher levels of mGluR2 mRNA in the PFC white matter. The expression of mGluR2, 3 in DA cells provide a mechanism for glutamate to modulate dopamine release in the human brain and this species-specific difference may be critical to understanding rodent models in schizophrenia.     

Up-regulation of Neurotensin mRNA in the Rat Striatum After Acute Methamphetamine Treatment

The effect of acute subcutaneous administration of methamphetamine on the expression of neurotensin mRNA was investigated in the adult rat striatum. At different time points (2, 6 and 24 h) following drug administration rats were killed, and mRNA levels were quantified both on films and emulsion-dipped tissue sections from two striatal levels. Two hours after methamphetamine injection, a dramatic increase in neurotensin mRNA levels was detected in different areas of the striatum at both rostral and caudal levels. Numerous positive cells were observed in the dorsomedial, dorsolateral and ventrolateral parts of the striatum. This up-regulation reflected an increase both in the number of cells expressing neurotensin mRNA and in the mean mRNA levels. This increase was still present after 6 h and was similar to the 2 h treated group at the rostral level of the striatum, but lower at the caudal one. Twenty-four hours after methamphetamine injection, neurotensin mRNA levels were back to control values, or in some areas even below. A strong increase in neurotensin mRNA-expressing cells was also seen in the olfactory tubercle, and the time-course was similar to the one observed in the striatum. In a second set of experiments, the effect of methamphetamine was evaluated on adjacent striatal sections hybridized with probes directed against neurotensin and substance P mRNAs, respectively. Two hours after drug administration, a significant increase in the levels of both peptide mRNAs was observed (+ 190% for neurotensin, +80% for substance P). These results demonstrate that methamphetamine is able to induce a dramatic, rapid and transient increase in striatal neurotensin mRNA levels, which may partly account for the elevation in neurotensin peptide levels observed in the striatonigral pathway after methamphetamine. The different anatomical localization of neurotensin mRNA-expressing cells observed after haloperidol and methamphetamine treatments, as well as the fact that the D1 receptor antagonist SCH-23390 is able to counteract the effect of methamphetamine but not that of haloperidol on neurotensin mRNA expression, suggests that there are at least two different subpopulations of neurotensin cells in the striatum. One population is regulated via D1 receptors and projects to the substantia nigra pars reticulata. The second is sensitive to D2 receptor stimulation and may project to the globus pallidus and/or may represent interneurons.     

The distribution of the mRNA and protein products of the melanin-concentrating hormone (MCH) receptor gene, slc-1, in the central nervous system of the rat

Melanin-concentrating hormone (MCH), a 19 amino acid cyclic peptide, is largely expressed in the hypothalamus. It is implicated in the control of general arousal and goal-orientated behaviours in mammals, and appears to be a key messenger in the regulation of food intake. An understanding of the biological actions of MCH has been so far hampered by the lack of information about its receptor(s) and their location in the brain. We recently identified the orphan G-protein-coupled receptor SLC-1 as a receptor for the neuropeptide MCH. We used in situ hybridization histochemistry and immunohistochemistry to determine the distribution of SLC-1 mRNA and its protein product in the rat brain and spinal cord. SLC-1 mRNA and protein were found to be widely and strongly expressed throughout the brain. Immunoreactivity was observed in areas that largely overlapped with regions mapping positive for mRNA. SLC-1 signals were observed in the cerebral cortex, caudate-putamen, hippocampal formation, amygdala, hypothalamus and thalamus, as well as in various nuclei of the mesencephalon and rhombencephalon. The distribution of the receptor mRNA and immunolabelling was in good general agreement with the previously reported distribution of MCH itself. Our data are consistent with the known biological effects of MCH in the brain, e.g. modulation of the stress response, sexual behaviour, anxiety, learning, seizure production, grooming and sensory gating, and with a role for SLC-1 in mediating these physiological actions.     

神经肽Y受体在人垂体腺瘤中的基因表达

目的研究NPY受体在人垂体腺瘤中表达及其规律。方法收集2004年1月~2005年8月期间我院神经外科手术切除垂体腺瘤获取标本57例。通过巢式聚会酶链反应(N-PCR)测定NPY的Y1R和Y2R受体。结果不同类型垂体腺瘤中均有NPY的Y1R、Y2R mRNA表达。Y1R基因表达的差异无统计学意义(F=1.97,P=0.098);Y2R表达的差异有显著统计学意义(F=2.703,P=0.03)。NPY与Y2R呈正相关(r=0.414,P=0.003),但与Y1R无相关性(r=-0.123,P=0.405),且Y1R与Y2R之间也无相关性(r=0.158,P=0.284)。PRL腺瘤中Y2R的表达明显低于GH腺瘤和促性腺瘤。GH腺瘤中NPY与Y2R表达呈正相关(r=0.558,P=0.025)。结论垂体腺瘤中存在NPY和Y1R及Y2R表达;Y2R表达的差异有显著统计学意义。Y2R在GH腺瘤和促性腺细胞腺瘤中的表达水平明显高于PRL腺瘤,而Y1R的表达无显著性差异。NPY受体的表达差异可能与不同类型垂体腺瘤的发生、发展及其内分泌行为有关。     

Role of Neuropeptide Y in the Regulation of Tyrosine Hydroxylase Messenger Ribonucleic Acid Levels in the Male Rat Arcuate Nucleus as Evaluated by in situ Hybridization

Neuroanatomical data have clearly demonstrated the existence of synaptic contacts between neuropeptide Y (NPY) endings and tuberoinfundibular dopaminergic (TIDA) neurons in the rat arcuate nucleus. In order to determine the influence of NPY in the biosynthesis of dopamine, we have studied the effects of NPY and some NPY analogs on tyrosine hydroxylase (TH) gene expression in TlDA neurons in the male rat. The following peptides: NPY, PYY, [Leu³¹, Pro³⁴]-NPY (a Y, receptor agonist) and NPY_13–36 (a Y₂ receptor agonist) were injected into the left lateral ventricle of adult male rats. All the animals were perfused with 4% paraformaldehyde 4 h after injection. Cryostat sections through the arcuate nucleus were processed for quantitative in situ hybridization. The intracerebroventricular injection of NPY, PYY and [Leu³¹, Pro³⁴]-NPY induced an increased of 43, 33 and 42%, respectively, in the number of grains overlying TH neurons. On the other hand, the Y₂ receptor agonist NPY_13–36 did not influence mRNA levels. These data then strongly suggest that NPY positively regulates the genetic expression of TH in rat TlDA neurons via the Y, NPY receptor subtype.     

Distribution of a Y1 receptor mRNA in the brain of two lamprey species,the sea lamprey (Petromyzon marinus) and the river lamprey (Lampetra fluviatilis)

The neuropeptide Y system consists of several neuropeptides acting through a broad number of receptor subtypes, the NPY family of receptors. NPY receptors are divided into three subfamilies (Y1, Y2, and Y5) that display a complex evolutionary history due to local and large‐scale gene duplication events and gene losses. Lampreys emerged from a basal branch of the tree of vertebrates and they are in a key position to shed light on the evolutionary history of the NPY system. One member of the Y1 subfamily has been reported in agnathans, but the phylogenetic tree of the Y1 subfamily is not yet clear. We cloned the sequences of the Y1‐subtype receptor of Petromyzon marinus and Lampetra fluviatilis to study the expression pattern of this receptor in lampreys by in situ hybridization and to analyze the phylogeny of the Y1‐subfamily receptors in vertebrates. The phylogenetic study showed that the Y1 receptor of lampreys is basal to the Y1/6 branch of the Y1‐subfamily receptors. In situ hybridization showed that the Y1 receptor is widely expressed throughout the brain of lampreys, with some regions showing numerous positive neurons, as well as the presence of numerous cerebrospinal fluid–contacting cells in the spinal cord. This broad distribution of the lamprey Y1 receptor is more similar to that found in other vertebrates for the Y1 receptor than that of the other members of the Y1 subfamily: Y4, Y8, and Y6 receptors. Both phylogenetic relationship and expression pattern suggest that this receptor is a Y1 receptor. J. Comp. Neurol. 521:426–447, 2013. © 2012 Wiley Periodicals, Inc.     

Neuropeptide Y Y1 receptor hippocampal overexpression via viral vectors is associated with modest anxiolytic-like and proconvulsant effects in mice

Neuropeptide Y (NPY) exerts anxiolytic- and antidepressant-like effects in rodents that appear to be mediated via Y1 receptors. Gene therapy using recombinant viral vectors to induce overexpression of NPY in the hippocampus or amygdala has previously been shown to confer anxiolytic-like effect in rodents. The present study explored an alternative and more specific approach: overexpression of Y1 receptors. Using a recombinant adeno-associated viral vector (rAAV) encoding the Y1 gene (rAAV-Y1), we, for the first time, induced overexpression of functional transgene Y1 receptors in the hippocampus of adult mice and tested the animals in anxiety- and depression-like behavior. Hippocampal Y1 receptors have been suggested to mediate seizure-promoting effect, so the effects of rAAV-induced Y1 receptor overexpression were also tested in kainate-induced seizures. Y1 receptor transgene overexpression was found to be associated with modest anxiolytic-like effect in the open field and elevated plus maze tests, but no effect was seen on depression-like behavior using the tail suspension and forced swim tests. However, the rAAV-Y1 vector modestly aggravated kainate-induced seizures. These data indicate that rAAV-induced overexpression of Y1 receptors in the hippocampus could confer anxiolytic-like effect accompanied by a moderate proconvulsant adverse effect. Further studies are clearly needed to determine whether Y1 gene therapy might have a future role in the treatment of anxiety disorders.     

Cloning,phylogeny, and regional expression of a Y5 receptor mRNA in the brain of the sea lamprey (Petromyzon marinus)

The NPY receptors known as Y receptors are classified into three subfamilies, Y1, Y2, and Y5, and are involved in different physiological functions. The Y5 receptor is the only member of the Y5 subfamily, and it is present in all vertebrate groups, except for teleosts. Both molecular and pharmacological studies show that Y5 receptor is highly conserved during vertebrate evolution. Furthermore, this receptor is widely expressed in the mammalian brain, including the hypothalamus, where it is thought to take part in feeding and homeostasis regulation. Lampreys belong to the agnathan lineage, and they are thought to have branched out between the two whole‐genome duplications that occurred in vertebrates. Therefore, they are in a key position for studies on the evolution of gene families in vertebrates. Here we report the cloning, phylogeny, and brain expression pattern of the sea lamprey Y5 receptor. In phylogenetic studies, the lamprey Y5 receptor clusters in a basal position, together with Y5 receptors of other vertebrates. The mRNA of this receptor is broadly expressed in the lamprey brain, being especially abundant in hypothalamic areas. Its expression pattern is roughly similar to that reported for other vertebrates and parallels the expression pattern of the Y1 receptor subtype previously described by our group, as it occurs in mammals. Altogether, these results confirm that a Y5 receptor is present in lampreys, thus being highly conserved during the evolution of vertebrates, and suggest that it is involved in many brain functions, the only known exception being teleosts. J. Comp. Neurol. 522:1132–1154, 2014. © 2013 Wiley Periodicals, Inc.     

Neuropeptide Y Y1 receptor mRNA in rodent brain: distribution and colocalization with melanocortin-4 receptor

The central neuropeptide Y (NPY) Y1 receptor (Y1-R) system has been implicated in feeding, endocrine, and autonomic regulation. In the present study, we systematically examined the brain distribution of Y1-R mRNA in rodents by using radioisotopic in situ hybridization histochemistry (ISHH) with a novel sensitive cRNA probe. Within the rat hypothalamus, Y1-R-specific hybridization was observed in the anteroventral periventricular, ventromedial preoptic, suprachiasmatic, paraventricular (PVH), dorsomedial, ventromedial, arcuate, and mamillary nuclei. In the rat, Y1-R mRNA expression was also seen in the subfornical organ, anterior hypothalamic area, dorsal hypothalamic area, and in the lateral hypothalamic area. In addition, Y1-R hybridization was evident in several extrahypothalamic forebrain and hindbrain sites involved in feeding and/or autonomic regulation in the rat. A similar distribution pattern of Y1-R mRNA was observed in the mouse brain. Moreover, by using a transgenic mouse line expressing green fluorescent protein under the control of the melanocortin-4 receptor (MC4-R) promoter, we observed Y1-R mRNA expression in MC4-R-positive cells in several brain sites such as the PVH and central nucleus of the amygdala. Additionally, dual-label ISHH demonstrated that hypophysiotropic PVH cells coexpress Y1-R and pro-thyrotropin-releasing hormone mRNAs in the rat. These observations are consistent with the proposed roles of the central NPY/Y1-R system in energy homeostasis.     

The effects of acute phencyclidine treatment on neuropeptide Y (NPY) neuronal system in the rat arcuate nucleus studied by immunocytochemistry and in situ hybridization

Summary Phencyclidine (PCP) is a dissociative drug and an antagonist of N-methyl-D-aspartate (NMDA) receptor. The effects of PCP treatment on neuropeptide Y (NPY) system in the arcuate nucleus of the rat hypothalamus were examined both by immunocytochemistry and in situ hybridization. In acute PCP-treated rats, the NPY-immunoreactive perikarya appeared in the arcuate nucleus but no perikarya were detected in controls, without colchicine pretreatment. The signals of NPY mRNA by in situ hybridization increased in the PCP-treated rats than those of controls. These results suggest that the NPY system in the arcuate nucleus might be partly controlled by glutamatergic neurons.     

Chronic Dizocilpine Maleate (MK-801) Treatment Suppresses the Effects of Nigrostriatal Dopamine Deafferentation on Enkephalin but not on Substance P Expression in the Rat Striatum

The present study examined the effects of chronic treatment with dizocilpine maleate (0.2 mg/kg i.p., twice a day for 8 days) alone or in combination with unilateral 6-hydroxydopamine-induced lesion of the nigrostriatal dopaminergic neurons on substance P and enkephalin expression in the rat striatum. This was done by means of quantitative in situ hybridization histochemistry and immunocytochemistry. As reported previously, the unilateral dopaminergic lesion resulted in marked decreases in substance P mRNA expression and immunoreactivity in the ipsilateral striatum, while enkephalin mRNA expression and Met-enkephalin immunoreactivity were considerably increased in this structure. Blockade of NMDA receptors by chronic dizocilpine maleate treatment alone resulted in decreased levels of striatal substance P mRNA without significant change in substance P immunoreactivity versus controls. Enkephalin mRNA levels were also decreased in the striatum, matched by parallel reductions in Met-enkephalin immunoreactivity. These observations indicate that NMDA receptor activity may exert tonic excitatory effects on substance P and enkephalin expression in the striatum. The same chronic treatment with dizocilpine maleate started 12 days after the 6-hydroxydopamine injection suppressed the lesion-induced up-regulation of enkephalin expression without significantly affecting the down-regulation of substance P expression. These data provide evidence that NMDA receptor-mediated mechanisms contribute to the alteration of striatal enkephalin expression associated with dopaminergic depletion in hemiparkinsonian rat models.     

人体血浆和垂体腺瘤组织中的神经肽Y含量及其临床意义

目的 :研究垂体腺瘤患者血浆和肿瘤组织中的神经肽Y(NPY)浓度与垂体腺瘤的关系。方法 :放射免疫分析方法测定 3 3例垂体腺瘤组织和 2 0例病人血浆的NPY浓度。结果 :不同类型垂体腺瘤组织中NPY含量有显著差别 ,侵袭性垂体腺瘤NPY含量高于非侵袭性垂体腺瘤。肿瘤组织与血浆NPY水平呈正相关。结论 :不同类型垂体腺瘤组织和血浆中NPY含量有显著差别 ,NPY水平可作为垂体腺瘤侵袭性的参考指标之一     

Bilateral 6-Hydroxydopamine-induced Lesion of the Nigrostriatal Dopamine Pathway Reproduces the Effects of Unilateral Lesion on Substance P but not on Enkephalin Expression in Rat Basal Ganglia

This study compared the effects of unilateral and bilateral 6-hydroxydopamine-induced lesions of the nigrostriatal dopaminergic neurons on substance P and enkephalin expression in the rat striatum and its main target structures by means of quantitative in situ hybridization and immunocytochemistry. In animals with bilateral lesion, substance P mRNA levels were decreased in the striatum, and this was matched by parallel reductions in substance P immunoreactivity in the striatum and in the striatonigral terminals at substantia nigra level in both hemispheres. These changes were similar to those observed ipsilaterally to unilateral lesion. In contrast, whereas increased striatal enkephalin immunoreactivity and mRNA levels and decreased immunoreactivity in the globus pallidus were observed on the lesioned side after unilateral lesion, no significant change in these enkephalin markers occurred in animals with bilateral lesion. These data suggest that the effects of dopamine deafferentation on substance P expression in the striatonigral system may be due primarily to removal of direct dopamine influence, whereas the effects on enkephalin expression in the striatopallidal system may involve complex interhemispheric adaptive mechanisms. The present finding that bilateral dopamine lesion does not simply reproduce the effects of unilateral lesion but creates a new functional state may have a critical bearing on the understanding and treatment of Parkinson's disease.     

Expression of the melanin-concentrating hormone (MCH) receptor mRNA in the rat brain

The melanin-concentrating hormone (MCH) system is thought to be an important regulator of food intake. Recently the orphan G protein-coupled receptor SLC-1 was identified as the MCH receptor (MCHR). Preliminary analyses of MCHR mRNA distribution have supported a role for the MCH system in nutritional homeostasis. We report here a complete anatomical distribution of the MCHR mRNA. We have found high levels of expression of MCHR mRNA in most anatomical areas implicated in control of olfaction, with the exception of the main olfactory bulb. Dense labeling was also detected in the hippocampal formation, subiculum, and basolateral amygdala, all of which are important in learning and memory, and in the shell of the nucleus accumbens, a substrate for motivated behavior and feeding. Within the hypothalamus, MCHR mRNA was moderately expressed in the ventromedial nucleus, arcuate nucleus, and zona incerta, all of which serve key roles in the neuronal circuitry of feeding. In the brainstem, strong expression was observed in the locus coeruleus, which is implicated in arousal, as well as in nuclei that contribute to orofacial function and mastication, including the facial, hypoglossal, motor trigeminal, and dorsal motor vagus nuclei. In most regions there was a good correspondence between MCHR mRNA distribution and that of MCH-immunoreactive fibers. Taken together, these data suggest that MCH may act at various levels of the brain to integrate various aspects of feeding behavior. However, the extensive MCHR distribution throughout the brain suggests that this receptor may play a role in other functions, most notably reinforcement, arousal, sensorimotor integration, and autonomic control.     

Increased Expression of NGFI-A mRNA in the Rat Striatum Following Burst Stimulation of the Medial Forebrain Bundle

Using in situ hybridization, we examined the mRNA expression for several immediate early genes in dopamine-innervated brain areas following electrical burst vs. regular stimulation of the medial forebrain bundle in anaesthetized rats. Two hours after 5 Hz burst stimulation, the expression of the nerve growth factor-inducible clone A (NGFI-A) mRNA was increased in the medial part of the striatum. This increase was prevented by pretreatment with the dopamine-D1 receptor antagonist, SCH23390 (0.1 mg/kg i.p.). After 8 Hz burst stimulation, NGFI-A mRNA expression was increased in the medial, central and lateral parts of the striatum. Induction occurred predominantly in cells expressing mRNAs for the dopamine-D1 receptor, substance P and dopamine and CAMP-regulated phosphoprotein (DARP-32). Regular stimulation had no effect on NGFI-A mRNA expression. The induction of NGFI-A was related to the levels of dopamine released by burst or regular stimulation as demonstrated with in vivo amperometry. Two hours after stimulation, the expression of none of the other genes studied was altered. One hour after 8 Hz burst stimulation, the expression of NGFI-A, NGFI-B and jun-B mRNAs was increased in the striatum and that of NGFI-A, NGFI-6, c-fos, fos -B and jun -B mRNAs was variably increased in the nucleus accumbens and lateral septum. These results provide additional support for the physiological importance of burst firing activity in midbrain dopamine neurons for the activation of their target cells. They demonstrate a spatial and temporal specificity as regards the brain region, the gene activated, the receptor involved and the phenotype of the cells affected.     

戊四氮致痫大鼠不同脑区神经肽Y的表达及意义

目的研究神经肽Y(neuropeptideY,NPY)在戊四氮(pentylenetetrazol,PTZ)致痫大鼠不同脑区中的变化,以探讨NPY与癫痫的关系。方法清洁级近交系雄性SD大鼠50只,分为对照组(A组,n=10)及实验组(40只)。实验组按体重50mg/kg经腹腔注射PTZ1次,对照组腹腔注射同等容量的生理盐水。根据癫痫发作分级,0~1级7只为B组,立即取脑;2级以上发作33只,随机于癫痫发作后0(C组,n=10)、6(D组,n=11)、24(E组,n=10)、72h(F组,n=2)取脑。采用放射免疫方法动态观察脑组织中海马、中脑、纹状体和额叶中NPY的改变;SP免疫组化染色法染色,观察各组大鼠海马CA1区NPY的表达。结果B组中脑、纹状体及额叶NPY含量较A组升高(P<005),而两组间海马NPY含量差异无显著性;癫痫发作组(C组、D组、E组)各部位NPY含量均明显高于A组。动态观察结果显示,癫痫发作后在中脑、海马、纹状体和额叶的NPY含量明显增高随后呈逐步下降,在癫痫发作后24h其含量与未发生惊厥的B组NPY含量差异无显著性(P>005);免疫组化染色显示癫痫大发作后海马NPY的表达明显增加,但随着时间的推移而降低。结论NPY与大鼠癫痫的发生、发展有密切关系。